Arrhythmia is a disease which is caused by dysfunction of ion channel due to abnormality of the channel gene or acquired diseases, by of artificial pathologic condition or by the remodeling of the channel inducing change of structure or expression. As a therapeutic agent of arrhythmia, local anesthetics (e.g., lidocaine and the like), β receptor blockers (e.g., propranolol and the like), and calcium channel blocker (e.g., verapamil or the like) are now used. The other agents include Na channel inhibitors, Ca channel inhibitors, and Na—H exchange inhibitors.
Possibility of lysophospholipid inducing arrhythmia is described in Coron. Artery Dis. 8, 19-27 (1997) without any description about cPLA2 inhibitors.
As cPLA2 inhibitors are disclosed indole derivatives (WO98/08818), benzene derivatives (EP544488, JP Laid-Open No.286852/93), trifluoromethylketone derivatives (JP Laid-Open No.268153/97), azaspiro derivatives (JP Laid-Open No.110835/97), pyrrolidine derivativs (WO97/05135, WO98/33797) and the like. However, there is no concrete description therein about the utility of these compounds for treating or preventing arrhythmia.